Relation of resting membrane polarization and insulin resistance in critically ill patients

Introduction Critically ill patients feature depolarization of the resting membrane potential and reduced membrane excitability in motor nerve and muscle [1,2], which is correlated to ICU-acquired weakness and an increased insulin resistance [3]. Objectives Since insulin is one agonist of the Na-K-pump, controlling resting membrane potential in muscle and nerve, we hypothesized that insulin resistance is linked to motor nerve resting membrane depolarisation in critically ill patients. Methods We recorded compound motor action potential from the abductor pollicis brevis muscle in ICU patients to test excitability measures of the median-nerve at baseline and during euglycemic-hyperinsulinemic clamp, proving resting membrane polarization. The recovery-of-excitability following a supra-maximal conditioning stimulus was tested at 18 conditioning test intervals, decreasing from 200 to 2 ms in geometric progression. Insulin sensitivity index (ISI), as marker of myocellular insulin resistance, was calculated during steady state condition of euglycemic-hyperinsulinemic clamp. Results 10 ICU patients and 31 healthy controls were enrolled in this trial. Compared to control group, ICU-patients exhibited depolarization of resting membrane potential (superexcitability in healthy controls -25 + 6.1% versus -18.5 + 4.5% in ICU patients; p = 0.003). The resting membrane depolarization was significantly correlated to ISI (R² = 0.858; p = 0.003), where pronounced insulin resistance correlates with pronounced resting membrane depolarization (Figure 1), indicating that membrane repolarization after insulin stimulation of Na-K-pump is reduced in patients with severe insulin resistance. K+ plasma levels were not correlated with membrane depolarization. Conclusions Resting membrane depolarization in critically ill patients is correlated to insulin resistance. Patients with severe insulin resistance reveal a failure of repolarization, so that high dosage of insulin administration does not facilitate rectification of membrane polarization.